Recently, there has been an outbreak of a typical pneumonia in Guangdong province in mainland China. Between November 2002 and March 2003, there were 792 reported cases with 31 fatalities (WHO. Severe Acute Respiratory Syndrome (SARS) Weekly Epidemiol. Rec. 2003; 78: 86). In response to this crisis, the Hospital Authority in Hong Kong has increased the surveillance on patients with severe a typical pneumonia. In the course of this investigation, a number of clusters of health care workers with the disease were identified. In addition, there were clusters of pneumonia incidents among persons in close contact with those infected. The disease was unusual in its severity and its progression in spite of the antibiotic treatment typical for the bacterial pathogens that are known to be commonly associated with a typical pneumonia.
The first SARS pandemic of the new millennium has affected 8,422 people with 916 fatalities [World Health Organization, Summary table of SARS by country, Nov. 1, 2002 to Aug. 7, 2003. Available at: http://www.who.int/csr/sars/country/en/country2003—08—15.pdf. Accessed Sep. 30, 2003]. A new hSARS virus was consistently isolated from those patients who seroconverted specifically to the virus and confirmed to reproduce SARS in a primate model [Fouchier R A et al., “Aetiology: Koch's Postulates fulfilled for SARS virus.” Nature 2003; 423:240; Kuiken T et al., “Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome.” Lancet 2003; 362:263-70]. Though the pandemic has been successfully contained with quarantine and infection control measures, the presence of this virus in wild game food animals [Guan Y et al., “Isolation and characterization of viruses related to the SARS coronavirus from animals in Southern China.” Science 2003; 302:276-78] and possible seasonality of this disease suggest that recurrence of such an epidemic is likely. Since all age sectors are affected and a high fatality is noted in the elderly and those with co-morbidities [Donnelly C A et al., “Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.” Lancet 2003; 361:1767-72], there is an urgent need to find a cure.
Prospective clinical and viral load studies in nasopharyngeal secretions from SARS patients showed that viral replication peaked at the tenth day after the onset of symptoms [Peiris J S et al., “Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.” Lancet 2003; 361:1767-72]. This viral replicative phase is followed by an immune control phase with decrease of viral load and concomitant appearance of specific neutralizing antibody. However, about one third of the patients continued to go into respiratory failure due to diffuse alveolar damage during this immune control phase, which suggests that part of the damage is related to immunodysregulation [Nicholls J M et al., “Lung pathology of fatal severe acute respiratory syndrome.” Lancet 2003; 361:1773-8].
At the moment, there are no commercially available antiviral agents which are tailor-made for the hSARS viruses. Thus, there is an urgent need to search for an agent for use in clinical and toxicity profile so that a randomized placebo control of SARS may be achieved by epidemiological measures, antiviral prophylaxis or treatment, and vaccination. During the last pandemic of SARS, the only available means for control were public health measures such as isolation of suspected cases, quarantine of contacts, and personal protective infection control procedures for high-risk individuals such as health care workers. There is an urgent need to find effective antiviral agents with acceptable side effect profiles. In developing countries such as China, commercially available western medicine with antiviral effects is unlikely to be affordable by most people. Moreover, the SARS mortality of Mainland China was only 7% which compared favorably with the 15 to 27% of other areas. Control trials can be conducted if the epidemic recurs in the coming winter.